Cardioactive steroids (CAS) remain in wide use throughout the world, although their benefits have become more and more restricted. Some of the most remarkable poisonings occur with exposures to plants such as Digitalis purpurea and Nerium oleander containing CAS, which are used by herbalists for varied disorders. Recent abuse of dried toad secretions from Bufo spp has lead to deaths with typical CAS morbidity and very high mortality. Rapid recognition of the CAS toxidrome and appropriate use of digoxin-specific antibody fragments can prove lifesaving.
There is evidence in the Ebers Papyrus (Papyrus Smith) that the Egyptians used plants containing CAS at least 3000 years ago. However, it was not until 1785, when William Withering wrote the first systemic account about the effects of the foxglove plant, that the use of CAS was more widely accepted into the Western apothecary. Foxglove was initially used as a diuretic and for the treatment of "dropsy" (edema), and Withering eloquently described its "power over the motion of the heart, to a degree yet unobserved in any other medicine.124
Subsequently, CAS became the mainstay of treatment for congestive heart failure and to control the ventricular response rate in atrial tachydysrhythmias. Because of their narrow therapeutic index and widespread use, both acute and chronic toxicity remain important problems.84 According to the American Association of Poison Control Centers data, between the years 2002 and 2006, there were approximately 8000 exposures to CAS-containing plants with no attributable deaths and about 14,000 exposures to CAS-containing xenobiotics resulting in 100 deaths (see Chap. 135).
Toxicity is typically encountered in very young and very old individuals. In children, most acute overdoses are unintentional, resulting from dosing errors (this is particularly pertinent with the use of digoxin because the submilligram doses make dose calculations subject to 10-fold [decimal point] errors), or mistakenly ingesting an adult's medication. Older adults are at particular risk for toxicity, either from interactions of the CAS with other medications in their chronic regimen or indirectly as a consequence of an alteration in the absorption or elimination kinetics. Drug—drug interactions from an adult's polypharmacy or from additional acute care xenobiotics that change CAS clearance in the liver or kidney, may alter protein binding and may result in increased bioavailability.
The most commonly prescribed CAS in the United States is digoxin; other internationally available but much less commonly used preparations are digitoxin, ouabain, lanatoside C, deslanoside, and gitalin. CAS toxicity may also result from exposure to certain plants or animals. Documented plant sources of CAS include oleander (Nerium oleander); yellow oleander (Thevetia peruviana), which has been implicated in the suicidal deaths of thousands of patients in Southeast Asia26, foxglove (Digitalis spp), lily of the valley (Convallaria majalis), dogbane (Apocynum cannabinum), and red squill (Urginea maritima). CAS poisoning may result from teas containing seeds of these ...